Monooxy-omega-aminoacetophenone derivatives



; UNITED? STATE llll Patented Aug. 7, 1928. r v

s "PATENT; OFFICE,

HELMUT LEGEBLOTZ, F BERLIN, GERMANY.

MONOOXY- L-AMINOACETOPHENONE DERIVATIVES.

No Drawing. Application filed March 23, 1927. Serial No. 177,829, and inAustria March 22, 1926.

This invention relates to certain derivatives ofmonohy-dr0xy-m-aininoacetophenones which are intended for use asstarting mate rials in the manufacture of other compounds havingvaluable therapeutical properties.

mula V CO.CH2.NRP.(l) CuH4 OX.(2, 3 or 4) in which R means hydrogen or amonovalent hydrocarbon radical, R" means a mono valent hydrocarbonradical and X means hydrogen or a monovalent hydrocarbon radical.

i is indicated by the numerals in parentheses, the substituentsof thenucleus may be either in ortho position or in meta or para position toeach other.

for manufacturing the said derivatives.

According to this invention the said de- (Hal meaning a halogen and Xmeaning bydrogen or a monovalent hydrocarbon radical) with monoordialkylamines (including aralkyl substitution products, suchasibenzyla-mine) or monoor diarylamines or mixed amines in Which onealkyl (or aralkyl) and onearyl substituent is contained.

In this reaction the corresponding hydrohalogenic acids are split offandbound to/an excess of the amine present and from the reaction mixturethe compounds carrying substituents in the amino group as above.referred tomay be separated.

The derivatives having the general for on (2,3or 4 in which there is nosubstituent in the hydrog yl group, can also be prepared by using asstarting materials acyloxy-w-halogenacetophenoneshaving the. generalformula;

oo.on2.na1(1 y I \oiacma u inwhich for the hydrogen atomjor the hy- Thesaid derivatives have the general ,for-

The invention further refers to processes droxyl group an acid radicalis substituted, and acting on these compounds with thesubstituted aminesabovereferred to. The acid radical is split off either during or afterthe reaction.

Example 1-19. grams of p-hydroxy-wbromacetophenone are dissolved incubic centimeters of alcohol of 96% strength and to tl1is.solution 40cubic centimeters of an aqueous methylamine solution of about 40%strength are gradually added in small portions, the reaction mixturebeing Well cooled. After 24 hours standing at ordinary temperature andpartly evaporating the excess of methylamine, the crystalline depositobtained is separated from the solution on a suction filter and Washedwith alcohol. The phydroXy-w-1nethylaminocacetophenone obtained andhaving the structural formula Cull; I

is purified by redissolving one ortwo times with alcohol and then formsbrilliant colour-V less leaflets having the meltino point of 147-- 148C. These leaflets can also. be obtained 'by precipitation with ammoniafrom the aqueous solution of the hydrochloride of the base. Thishydrochloride when crystallized from alcohol forms crystals having themelting point 239240 C.

Ezrample 2.2.15 grams of p-hydroxy- 'w-bI'OHlitCGtOPllGDOIIB aredissolved in ben- J zene and to. this solution 1.46 grams ofdiethylamine are added. After about half an hours standing the solutionis separated upon, after some time p-hydroxy-wdiethylamino'acetophenonehaving the structural formula is separated in compact er stalline druseshaving a melting pointer-1 7 478 C.

' Example 3.- 5 grams of 'p-methoxy-o bromacetophenone are made intosuspension" with 3 cubic centiinetersbf a1c0hol of 96 %I structuralformula.

. suction filter and transformed into its hydro- Example 4.42 grams ofp-benzoyloxy-ebromacetophenone are made into suspension with 50 cubiccentimeters of alcohol of 96% strength and 50 cubic centimeters of anaqueous methylamine solution of 40% strength are then slowly addedwithin about 4.- hours while stirring and well cooling. When the mixtureis allowed to stand for some time, a crystalline mass is separated whichis increased when the alcohol is' evaporated. The crude base isseparated on a chloride which is purified byrre-dissolving andseparating it by means of alcohol ofstrength. The base obtained fromthis hydrochloride is p-hydroxy-w-methylaminoacetophenone having thestructural formula.

CO.CH1.NH.CHi(1) C0134 \oHu During the reaction the benzoyl group issplit off, benzoicacidethylester being formed.

Example 5.-6.4 grams of p-benzoyloxyw-bromacetoph-enone are agitatedduring some hours with 250 cubic centimeters of ether and 5 grams ofdiethylamine. The ethereal solution is separated from the precipitate ofdiethylaminehydrobromide and thep-benzoyloxy-w-diethyilaminoacetophenone having the structural formulais extracted from the solution by means of water to which hydrochloricacid has been added. This aqueous solution is then heated to boiling forabout one hour at a reflux cooler, the benzoic acid formed is removed bymeans of ether, to the hydrochloric solution an excess of ammoniaisadded and the p-hydroxy-w-dieth laminoacetophenon having the structuralormula f is extracted by means of ether. The residue obtained from theetheral solution is neutralized with hydrochloric acid and brought todryness and the remaining crystalline mass is purified by re-dissolvingand separating by means of alcohol, crystals ofp-hydroxy-w-diethylaminoacetophenonehydrochloride having the structuralformula being obtained which crystals have a melting point of 194 C.

What I claim is 1. The hereinbefore describedmonohydroxy-w-aminoacetophenone derivatives carrying substituents in theamino group and having the general formula in which R means hydrogen ora m'onovalent hydrocarbon radical, R means a monovalent hydrocarbonradical and X means hydrogen or a monovalent hydrocarbon radical.

2. The hereinbefore described process of preparing monohydroxy o)aminoacetophcnone derivatives carrying substituents in the amino groupand having the general formula CQCHg-NR'R" CaHa in which R means hydroen or a m'onoyalent hydrocarbon radical, means a monovalent hydrocarbonradical and X means hydrogen or a monovalent hydrocarbon radical, saidprocess consisting in acting upon hydroxy-w-halogenacetophenonederivatives having the general formula,

in which Hal means a halogen and X means hydrogen or a monovalenthydrocarbon radical with an amine having the general formula mem'n" inwhich R means hydrogen or a monovalent hydrocarbon radical and R" meansmonovalent hydrocarbon radical.

3.. The hereinbefore described process of I preparing monohydroxy aaminoacetophenone derivatives carrying substituents in the amino groupand having the general formula can on in which R means hydrogen or amonovalent hydrocarbon radical and 11 means a monovalent hydrocarbonradical, which acyl 1 monovalent hydrocarbon in which Hal means processconsists in acting upon acyloxym-halogenacetophenones having the generalformula GOSH-2.1151 CIHI in which Hal means a halogen and Ac an groupwith an amine having the general formula NH.R'R"

in which R means hydrogen or a monovalent hydrocarbon radical and Rmeans a monovalent hydrocarbon radical, the acyl group being split offduring the reaction.-

4. The hereinbefore described process of preparingmonohyd1'oxy-w-aminoacetophenone derivatives carrying substituents inthe amino group and having the general formula in which R means hydrogenor a monovalent hydrocarbon radical and R means a radical, which processconsists in acting upon acyloxy-ewhalogenacetophenones having thegeneral formula /CO- CHI-H81 a halogen and Ac an acyl group with anamine having the general formula mama" in which R means hydrogen or amonovalent hydrocarbon radical and R" means a V I mg monovalenthydrocarbon radical, and. then splitting ofi? the acyl group. 5, Thehereinbefore described 'p-hydroxyw methylaminoacetophenone having thestructural formula oo.on,.nn.cmo

and forming brilliant colourless leaflets havwhich process consists inacting in alcoholic suspension with methylamine onp-benzoyloxy-wbromacetophenone having the structural formula 00.0mm-CaHA 0.oo.o.H,

separating the crystalline mass from the reaction mixture and purifyingit by transforming it into a hydrochloride, recrystah lizing the latterand separating the base therefrom.

In testimony whereof I have aflixed my signature.

HELMUT LEGERLOTZ.

the melting point of 147-148 C. and

acetone or benzene,

